Chemoproteomics map shows where interferonopathy proteins can be hit by small molecules
- Published covalent chemoproteomics and structural data were pooled to find ligandable cysteines, tyrosines and lysines on proteins linked to Mendelian type I interferonopathies.
- Several actionable sites emerged, including on ADAR1, RNASEH2A and SAMHD1.
- The aim is to give immunotherapy teams starting points: raising interferon tone with such modulators might help anti-tumour immunity.
💡 Points Based on the abstract
This is a resource, not a validation: a ligandable residue says nothing about whether occupying it inhibits or activates the protein, and for loss-of-function disease genes like RNASEH2A and SAMHD1 the therapeutic direction is the opposite of what a covalent inhibitor does. I'd rank the sites by whether the target needs to be switched off for tumour immunity, which makes ADAR1 the obvious first to test with tool compounds.
Ligandability assessment of interferonopathy-associated proteins using chemoproteomics ↗